Does tobacco smoking influence the occurrence of hand eczema?

Background  Tobacco smoking is known to influence various inflammatory skin diseases and an association between tobacco smoking and hand eczema has been proposed in some studies.
Objectives  To examine a possible association between reported current tobacco smoking and the occurrence of hand eczema.
Subjects and methods  Previously collected questionnaire data on the occurrence of hand eczema in three occupational cohorts and corresponding controls from the general population were studied. The questionnaires used included questions on 1-year prevalence of hand eczema and questions on smoking habits. For one occupational group, hairdressers and their controls, information on amount of smoking was obtained. Information on age, sex and history of atopy was also available.
Results  In total, answers regarding smoking and hand eczema were obtained from 13 452 individuals. Out of 3493 smokers, 437 (12·5%) reported hand eczema compared with 1294 out of 9959 nonsmokers (13·0%) ( P  =   0·51). With regard to the number of cigarettes smoked, 22·6% of the hairdressers smoking more than 10 cigarettes per day reported hand eczema compared with 17·4% of those smoking 0–10 cigarettes per day ( P  =   0·01). Corresponding figures for the controls were 14·5% and 11·7%, respectively ( P  =   0·06).
Conclusions  No clear association was found between 1-year prevalence of hand eczema and smoking. Heavy smoking, more than 10 cigarettes per day, may give a slightly increased risk of hand eczema. Further studies with information on the amount of tobacco consumption and on possible confounders are needed to evaluate smoking as a risk factor for hand eczema.     

Can the immersion time of PUVA bath therapy be shortened?

Up to now, there are only a few data available concerning the influence of bathing time on skin phototoxicity. We compared the erythemal responses of normal skin to bath PUVA with 8-methoxypsoralen (8-MOP) after 5, 10 and 20 min immersion time. Currently, 20 min is the routinely performed immersion time in many European countries, including Germany, while in other countries bathing times are shorter. The minimal phototoxic dose (MPD) following immersion times of 5 min and 10 min in a warm water bath (37 degrees C) containing 1 mg/l 8-MOP was compared to the MPD following 20 min immersion time in a half-sided manner in a total of 24 patients. Our results revealed that an immersion time of 5 min did not yield a detectable erythema after 72 h. In contrast, both 10 and 20 min PUVA baths induced visible erythemas with a significantly higher median MPD following 10 min immersion (2.25 J/cm2) compared to 20 min baths (1.5 J/cm2). As an erythemal response of 8-MOP PUVA bath seems reduced after shorter immersion times, comparative studies on the clinical efficacy using shorter time regimens have to be conducted before conclusive recommendations for clinical PUVA-bathing time can be given.     

Does topical tacrolimus ointment enhance the efficacy of narrowband ultraviolet B therapy in vitiligo? A left–right comparison study

Background: Narrowband ultraviolet B (NB‐UVB) therapy has emerged as one of the most favored treatment options in patients with generalized vitiligo. The aim of combining topical agents is to improve the efficacy of NB‐UVB in causing repigmentation in vitiligo. Aims and objectives: The present study aims to study the effect of combining topical tacrolimus to NB‐UVB therapy in causing repigmentation in vitiligo lesions. Methods: This prospective single‐blind study was performed on 80 patients of generalized vitiligo above 12 years of age who had symmetrically distributed vitiligo lesions on the face, trunk or limbs. The patients applied topical tacrolimus 0.1% ointment twice daily on selected symmetrically distributed lesions on the left side of the body. No topical agent was applied on the corresponding lesions on the right side. The patients also received whole‐body NB‐UVB exposure three times every week on non‐consecutive days according to a set protocol. Lesions selected for the comparison analysis were photographed serially and assessed by a single‐blinded observer for the extent or repigmentation achieved. The extent of repigmentation achieved was calculated on the basis of VASI scoring. The time taken for the initial repigmentation to start, the overall repigmentation achieved as well as any adverse effects were noted down and compared between the selected lesions on the two sides. Results: Seventy‐four patients with 234 symmetrical vitiligo lesions were available for comparison analysis at the end of study period. The mean repigmentation achieved on the left‐sided study lesions was approximately 71% (VASI score of approximately 4.0) as compared with 60.5% on the symmetrically distributed right‐sided lesions (VASI score of 3.4). Moreover, the repigmentation started earlier on the study lesions on left side than on the right‐sided ones. No significant adverse events were reported with the combination treatment. Conclusions: Addition of topical tacrolimus increases the extent of overall repigmentation achieved with NB‐UVB therapy in vitiligo and also reduces the cumulative NB‐UVB dose needed to achieve a therapeutic benefit in affected patients.     

Is PUVA maintenance therapy necessary in patients with early‐stage mycosis fungoides? Evaluation of a treatment guideline over a 28‐month follow‐up

Background Cutaneous T‐cell lymphoma is a rare condition that represents 2% of all lymphomas and 75–80% of primary cutaneous lymphomas. The objective of the present study is to evaluate a clinical practice guideline. Methods This paper reports a prospective cohort study with a five‐year follow‐up. This is the second report to describe the analysis of data obtained during follow‐up of 28 months. To date, 40 patients diagnosed with early‐stage mycosis fungoides (stage IA, n = 20; stage IB, n = 20) have been enrolled. All patients have been treated with a minimum of 58 sessions of psoralen and long‐wave ultraviolet radiation, with complete clinical and histological clearance of lesions. Variables considered include disease duration, treatment time, treatment dose, and history of relapse. Complete physical examinations and diverse complementary examinations were performed. A tumor–node–metastasis–blood staging system was applied. The population was divided into two groups according to results consisting, respectively, of those who relapsed during follow‐up (n = 12) and those who did not (n = 28). Results History of relapse was the variable most strongly associated with future relapse (relative risk = 10.38, 95% confidence interval 2.64–40.72). No statistically significant difference between the groups according to receipt of maintenance therapy was found (P = 0.161). Conclusions Our results strongly suggest that maintenance therapy does not prevent future relapse. However, history of relapse is a strong predictor for future relapse.     

What's new in atopic eczema? An analysis of systematic reviews published in 2010–11

This review provides a summary of key findings from 24 systematic reviews of atopic eczema (AE) published or indexed between 1 August 2010 and 31 December 2011, updating published summaries from previous years. Epidemiological evidence points to the protective effects of early daycare, endotoxin exposure, consumption of unpasteurized milk, and early exposure to dogs, but antibiotic use in early life may increase the risk for AE. With regard to prevention of AE, there is currently no strong evidence of benefit for exclusive breastfeeding, hydrolysed protein formulas, soy formulas, maternal antigen avoidance, omega‐3 or omega‐6 fatty‐acid supplementation, or use of prebiotics or probiotics. With respect to AE treatments, the most compelling new systematic review evidence was for proactive treatment with topical anti‐inflammatory agents (topical corticosteroids and topical calcineurin inhibitors) for the prevention of AE flares in patients with moderate to severe AE. A meta‐analysis of 4 trials confirmed the superiority of tacrolimus 0.1% over pimecrolimus for the treatment of AE, and a review of 17 trials found that tacrolimus (0.1% or 0.03%) was broadly similar in efficacy to mild/moderate topical corticosteroids. Evidence for the role of education in the management of AE was less conclusive, with evidence from randomized controlled trials showing mixed results. Further work is needed in this area to conduct high‐quality trials of educational interventions that are clearly described and reproducible. There is no clear evidence for the efficacy of homeopathy, botanical extracts or Chinese herbal medicine in the treatment of AE, as large well‐designed trials are lacking in these areas.     

What’s new in atopic eczema? An analysis of systematic reviews published in 2009–2010

This review provides a summary of key findings from 18 systematic reviews on atopic eczema, published or indexed between January 2009 and 24 August 2010. There was no good evidence on the possible benefit of organic food consumption and eczema. Maternal intake of fish or fish oil may be associated with a reduced risk of eczema in offspring, although further studies are needed. There is some evidence that partially hydrolysed infant formulas rather than standard formulas may be associated with a reduced risk of eczema in infants, but there are shortcomings in the existing evidence. An inverse relationship has been found between gliomas/acute lymphoblastic leukaemia and allergic disease/eczema, but there appears to be no association between multiple sclerosis and eczema. Attention deficit hyperactivity disorder does appear to be associated with eczema, but there is no evidence of a causal link. The risk of eczema seems to be increased in urban compared with rural areas. Some new evidence has suggested superiority of 1% pimecrolimus over potent and mild corticosteroids at 6 months but not 12 months, and there is some evidence for superiority of 0.03% and 0.1% tacrolimus over 1% pimecrolimus. An updated Cochrane Review still found no evidence of a benefit from any form of antistaphylococcal treatment in managing clinically infected or uninfected eczema. The evidence base is poor for bath emollients, occlusive treatments (e.g. wet and dry wraps) and woven silk clothing in treating eczema. In general, the methods used in most systematic reviews of eczema need to be reported more clearly, especially with regard to a more vigorous quality assessment of included studies. Included studies are frequently heterogeneous, proxy reporting is common, and appropriate disease definitions are often lacking. Better adherence to existing guidance on trial reporting and prospective registration of clinical trials may help improve the quality of studies.     

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo‐controlled double‐blind study

BACKGROUND: Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo. OBJECTIVES: We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo. METHODS: Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated. RESULTS: Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively). CONCLUSIONS: Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.     

What’s new in atopic eczema? An analysis of the clinical significance of systematic reviews on atopic eczema published in 2006 and 2007

This review summarizes clinically important findings from 19 systematic reviews published between January 2006 and August 2007 on the topic of atopic eczema (AE). The evidence suggests that avoidance of allergenic foods during pregnancy or the use of hydrolyzed or soy formula milks does not prevent eczema. Delayed introduction of solids may decrease eczema risk. Asthma typically develops in around a third of children with eczema, and wheezing in early infancy is a predictor of risk. Established topical corticosteroids such as betamethasone should be used just once daily. Topical tacrolimus and pimecrolimus can be used for people who become dependent on topical corticosteroids, especially on sensitive sites such as the face. Wet wraps are useful in secondary care for inducing remission in a child, but they are not a treatment for mild eczema and they should not be used long term. Oral ciclosporin can be used for inducing a remission in severe eczema, and azathioprine can be considered for maintenance treatment. Narrowband ultraviolet (UV)B phototherapy can be used for chronic AE, and UVA1 may be useful for acute eczema. There is little convincing evidence of a clinical benefit with evening primrose oil for eczema, but there is some good new evidence that educational support to eczema families is beneficial. Future trials need to be larger, and include active comparators, patient-reported outcomes and longer-term aspects of disease control. They should be better reported, and registered on a public clinical trials register.     

Does collapse of immune privilege in the hair‐follicle bulge play a role in the pathogenesis of primary cicatricial alopecia?

Background. The hair‐follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which seem to restrict immune‐mediated injury in specific locations. As epithelial hair‐follicle stem cells (eHFSC) reside in the hair‐follicle bulge region, it is conceivable that these IP mechanisms protect this vital compartment from immune‐mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle. Primary cicatricial alopecias (PCA) are a group of inflammatory hair disorders that result in hair‐follicle destruction and permanent alopecia. Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions. Aim. To explore the possible role of bulge IP collapse in PCA pathogenesis. Methods. We report three clinically distinct cases of PCA. Immunohistochemical analyses of paired biopsies from lesional and uninvolved scalp skin were compared using recognized markers of IP. Results. Immunohistochemical investigation found increased expression of major histocompatibility complex (MHC) classes I and II and of β2‐microglobulin in the bulge region of lesional follicles compared with uninvolved follicles in each case. Further, expression of the bulge marker keratin 15 was reduced in lesional skin in two of the cases. Conclusions. This small series represents our first preliminary attempts to ascertain whether bulge IP collapse may play a role in PCA pathogenesis. We present standard parameters relating to hair‐follicle IP in the bulge region of three patients with distinct PCA variants, and show the presence of features consistent with bulge IP collapse in each case.     

Management of chronic spontaneous urticaria in real life – in accordance with the guidelines? A cross‐sectional physician‐based survey study

Background Recently, the updated EAACI/GA²LEN/EDF/WAO guidelines for urticaria have been published. Objective To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. Methods During this cross‐sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. Results A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first‐line treatments were non‐sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one‐third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. Conclusion The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care.     

What causes flares of eczema in children?

Summary Background Although eczema affects 2–20% of children worldwide, there is little direct evidence on the role of environmental factors in disease flares. Objectives We sought to identify which environmental factors might worsen eczema. Methods Sixty children aged 0–15 years with eczema were studied intensively for up to 9 months. Daily electronic diaries and portable data loggers were used to record indoor exposures, and external meteorological data were obtained from a local monitoring centre. The primary outcome was a daily ‘bother’ score. Autoregressive moving average models were used to study the impact of exposures on eczema severity for individuals. Random effects modelling pooled estimated regression coefficients across participants. Results Increased severity was associated with nylon clothing [pooled regression coefficient 0·23, 95% confidence interval (CI) 0·03–0·43], dust (0·53, 0·23–0·83), unfamiliar pets (0·22, 0·10–0·34), sweating (0·24, 0·09–0·39) and shampoo (0·07, 0·01–0·14). The latter was enhanced in cold weather (0·30, 0·04–0·57). Body‐site specificity was observed for nylon clothing, (trunk P =0·02, limbs P = 0·03), wool clothing (trunk P = 0·03, but not limbs P = 0·62) and unfamiliar pets (hands P < 0·001). A combination of any three of seven likely variables was associated with disease worsening (pooled regression coefficient 0·41, 95% CI 0·20–0·63). Conclusions This exploratory study suggests that nylon clothing, dust, unfamiliar pets, sweating and shampoos may play a direct role in worsening eczema in children with eczema. Combinations of exposures acting in concert may also be important. Such knowledge may be useful to families with eczema and could lead to better strategies for preventing flares.     

Can melatonin and its metabolites boost the efficacy of targeted therapy in patients with advanced melanoma?

Despite groundbreaking new treatments such as checkpoint inhibition and targeted therapy, the overall response and survival rates are limited in patients with metastatic melanoma. Here, we hypothesize that melatonin and its metabolites could be promising boosters of the efficacy of BRAF/MEK inhibitors in patients with advanced melanoma. Melatonin, a well-known endogenous synchronizer of the circadian biorhythm has a variety of promising effects for melanoma biology. It regulates proliferation, apoptosis and oxidative phosphorylation via melatonin receptors, and receptor-independent pathways due to its lipophilicity. By means of interfering with the above cellular pathways, melatonin and related compounds may alter the cAMP-PKA-MITF axis, modulate tumor cell metabolism, affect MAPK signalling pathway thereby enhancing the suppressive effect of BRAF/MEK inhibitors on melanoma cell growth, and survival. Such findings could fuel preclinical studies and clinical studies where melatonin or its metabolites are combined with targeted therapy to better treat patients with metastatic melanoma.